Inhibition of mg2+ extrusion attenuates glutamate excitotoxicity in cultured rat hippocampal neurons

Yutaka Shindo, Ryu Yamanaka, Kohji Hotta, Kotaro Oka

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Magnesium plays important roles in the nervous system. An increase in the Mg2+ concentration in cerebrospinal fluid enhances neural functions, while Mg2+ deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg2+ due to the release of Mg2+ from mitochondria, followed by a decrease to below steady-state levels. Since Mg2+ deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg2+ decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg2+ extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg2+ release from mitochondria and Mg2+ extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg2+ concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg2+ regulation in neuronal survival under excitotoxicity.

Original languageEnglish
Article number2768
Pages (from-to)1-14
Number of pages14
Issue number9
Publication statusPublished - 2020


  • Excitotoxicity
  • Fluorescence imaging
  • Magnesium
  • Neuroprotection

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics


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